Antineoplastic treatment regimens consisting of chemotherapy often result in a dysfunction of hematopoietic precursor cells of the granulocyte-macrophage (GM-CPU-C) lineage. We were, therefore, interested in testing the ability of selected biological response modifiers (BRMs) to modulate growth and differentiation of GM-CFU-C and nucleated bone marrow cells (BMC) in normal and cyclophosphamide (CY)-pretreated mice. In vivo treatment of normal mice with either MVE-2 or poly ICLC induced an increase in secretion of colony stimulating factor (CSF) by BMC and macrophages, which was followed by an increased proliferation rate of GM-CFU-C and BMC. Both BRMs were also able to ameliorate the bone marrow depressing effects of CY pretreatment and to induce significantly enhanced MPhi activities when given about 3 days after CY. The present results thus support the concept that selected BRMs might be of value in reconstituting granulocyte and macrophage functions. We are also in the process of identifying whether immortalized human T cells secrete growth factors essential for long-term growth of human pluripotent hematapoietic stem cells in vitro. Identification of such factors (e.g. multi-CSF) could provide a model for studying physiologic regulation of bone marrow cell growth and differentiation and could also allow to sustain proliferating stem cells in vitro as a source of autologous BMC after treatment with chemotherapy. We are further interested in autocrine regulation of tumor growth. We have preliminary evidence that two murine tumors (a Moloney virus-transformed T lymphoma and a spontaneous lung carcinoma) are secreting factors that stimulate their own growth in a clonogenic assay and in suspension culture. These findings could provide the basis for trying to interfere with the respective tumor growth, e.g. by inhibiting the factor(s) or their production.